Autoimmune Brain Disease
(AIBD)

Autoimmune Brain disease or "AIBD" consists of a syndrome of central nervous system which is caused
by antibodies or immune cells which are attacking the brain. There is considerable overlap between autoimmune disorders that attack the ear and those that attack the brain.

The immune system is complex and there are several ways
that it can damage the brain.

Traditional "autoimmune
diseases"

There are are also organ specific disorders
such as Hashimoto's thyroiditis and Celiac disease (sprue) which occasionally
are accompanied by AIBD. In Celiac disease, antibodies have been found directed against transglutamase 2 (an autoantigen in the gut), and transglutamase 6 - an antigen independent of intestinal involvement (Hadjivassilou M, et al, 2008).

Recently (2010), a new disorder called "CLIPPERS" Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids was described by Pittock et al. This disorder consists of an MRI pattern of blood vessel enhancement of the pons, combined with a variety of pontine symptoms -- facial paresthesia, diplopia, dysgeusia, and ataxia, and response to steroids. (Pittock et al, 2010). It points out the value of trying steroids in mysterious CNS disorders with signs of inflammation. We ourselves as well as most neuroradiologists attribute MRI like this to vascular malformations. It is possible that some of these cases actually have CLIPPERS (it would probably take an autopsy to be sure).

AIBD is rare, probably accounting for less than 1% of
all cases of central disturbances.

What causes autoimmune brain disease ?

The cause of AIBD is generally assumed to be related to
either antibodies or immune cells that cause damage to the brain. There are
several theories as to how these might arise, analogously to other putative
autoimmune disorders. It is also possible that they don't "cause" the problem, they are just associated with it. Or in other words, a positive test shows that there is an inappropriate immune response, but doesn't necessarily mean that it is causing a particular disease.

Mistaken identity: Just because there is a positive blood test in a particular disease, does not imply that one causes the other.

It might just be a coincidence (perhaps the case with Gluten sensitivity and Hashimoto's encephalitus, as these are conditions associated with extremely common auto-antibodies). Or there might be a common underlying cause of both the antibodies and the disease. This has been suggested to be the situation for the "classic paraneoplastic antigens", as in animal models, these antibodies seem to be innocuous (Balzabal-Carvallo and Jancovic, 2012).

Examples of antibodies in the "mistaken identity" class include Anti-Yo, anti-Tr, anti-Ri, and anti-Hu. In other words, the "classic" paraneoplastic antibodies, don't seem to "cause" anything.

On the other hand, there are also antibodies that are directed against cell-surface antigens. There is good evidence that these antibodies cause disease. These include VGKC antibodies, and NMDA-R antibodies. They are associated with teratomas primarily, and patients respond to removal of the tumor.

Other pathogenic antibodies are thought to be glycine receptor antibodies causing PERM (progressive encephalophy, rigidity and myoclonus). Hashimoto's encephalitis is also thought to be steroid responsive, suggesting that the antibodies are toxic, although the antibodies associated with Hashimotos are very common.

Potential mechanisms for brain injury from antibodies include:

Bystander damage: In this theory damage to the
brain causes cytokines to be released which provoke, after a delay, additional
immune reactions. This theory might explain the attack/remission cycle of disorders
such as multiple sclerosis.

Cross-reactions: In this theory, antibodies
or rogue T-cells cause accidental brain damage because the brain shares common
antigens with a potentially harmful substance, virus or bacteria that the body
is fighting off.

Intolerance: The brain, like the eye may be
only an partially "immune privileged" locus, meaning that the body
may not know about all of the brain antigens, and when they are released (perhaps
following surgery or an infection), the body may wrongly mount an attack on
the "foreign" antigen. In the eye, there is a syndrome called "sympathetic
ophthalmia", where following a penetrating injury to one eye, the other
eye may go blind. This theory is not presently in favor for the AIBD.

Genetic factors: There is increasing evidence that genetically
controlled aspects of the immune system may increase or otherwise be associated
with increased susceptibility to brain injury.

How is the diagnosis
of autoimmune brain disease made?

The diagnosis is based on history, findings on physical
examination, blood tests, and the results of other tests.

HBA1C (for diabetes, which is often autoimmune mediated
also, and is associated with anti-GAD)

How
is Autoimmune Brain Disease Treated ?

There are several protocols for treatment. In cases with
a classic rapidly progressive impairment, a trial of steroids (Prednisone or
Decadron) for 4 weeks may be tried. In persons with response to steroids, in
most cases a chemotherapy type of medication such as Cytoxan or Methotrexate
will be used over the long term ). Plasmapheresis or IVIG (immunoglobulin infusion)
may be beneficial. Newer medications are constantly being developed for immune suppression, usually aimed at tumors of the immune system.

Autoimmune brain disease is rare making it difficult
to study. One can speculate that there might be effective treatments that simply
have not been discovered. For example, there are numerous potential treatments
that have not been tried in a formal way.

Gamma globulin infusions, given monthly,
is useful in numerous autoimmune disorders. This treatment is very expensive,
which limits its use. Immune modulating drugs such as are used for treatment
of MS (beta-interferon, alpha-inteferon, copaxone) are commonly used. Rituximab has been used in opsoclonus where the eyes move to fast, as well as Miller-Fisher syndrome where the eyes don't move at all (go figure). Other
medications that have coincidental suppression of immune responses, such as
minocycline, might be tried.